JPH02235873A - Oxazolidinedione derivative and production thereof - Google Patents

Abstract

NEW MATERIAL:The oxazolidinedione derivative of formula I (R<1> is H or alkyl; R<2> is H or lower alkyl). EXAMPLE:3-(2-Fluoro-4-ethoxycarbonylmethyloxy-5-nitrophenyl)-5-isoprop yli- dene-1,3-oxazolidine-2,4-dione. USE:An intermediate for the ready production of a benzoxazinone derivative useful as a herbicide. PREPARATION:The compound of formula I can be produced by reacting 3-(2,4- difluoro-5-nitrophenyl)-5-isopropylidene-1,3-oxazoli-dine-2,4-dione with a compound of formula II in the presence of a base. A compound of formula III (R<3> is H, alkyl, cyanoalkyl, alkenyl, alkynyl or aralkyl) having high herbicidal activity can be produced from the subject compound in high yield.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention relates to the general formula (!) [wherein Rl represents a hydrogen atom or an alkyl group, and R
8 represents a hydrogen atom or a lower alkyl group. ] (hereinafter referred to as the compound of the present invention) and a method for producing the same. More specifically, the present invention provides compounds of the general formula (IN) useful as spinal active ingredients of herbicides [wherein R1 represents a hydrogen atom or a lower alkyl group, and R3 represents a hydrogen atom, an alkyl group, a cyanoalkyl group, an alkenyl group] group, alkynyl group, or aralkyl group. The present invention provides a manufacturing intermediate for a benzoxazinone derivative represented by the following formula and a method for manufacturing the same. [Prior art] Compounds represented by the general formula (In) are disclosed in Japanese Patent Application No. 63-2549.
It is a penzoxazinone derivative that exhibits herbicidal activity as described in Japanese Patent No. 2 and 63-25493, and is a compound that has high herbicidal activity against many weeds. [Problems to be solved by the invention] In producing the compound represented by the general formula (III), it is necessary to establish a simple production method that can obtain the desired compound in terms of yield and selectivity. ．． [Means for Solving the Problems] The present inventors have discovered that the general formula (II) has high herbicidal activity.
As a result of intensive studies on the method for producing the compound represented by I), it was discovered that the compound of the present invention represented by the general formula (1) is extremely important as an intermediate for its production. The present invention was completed by demonstrating that the target compound represented by general formula (III) can be easily produced. That is,
The compound (1) of the present invention is reacted under reducing conditions, and the reduction of the nitro group and the subsequent intramolecular condensation reaction with the carboxyl group or ester group are simultaneously proceeded to form a compound of the general formula (III).
') [In the formula, Rl represents the same meaning as above. ], and then the general formula (m R @" - Y (IV) [wherein R1 represents an alkyl group, a cyanoalkyl group, an alkenyl group, an alkynyl group, or an aralkyl group, and Y represents a leaving group.] by reacting with an electrophilic agent represented by the formula (II1'') in the presence of a base, the general formula (II1''
) [In the formula, R' and R1 have the same meanings as above. ] can be produced. Next, the method for producing the compound of the present invention will be described in detail. The compound of the present invention is composed of 3-(2,4-difluoro-5-ditrophenyl)-5-isoprohylidene-1,3-oxazolidine-2,4-dione and the general formula [wherein R1 and R
t has the same meaning as above. It can be produced by reacting 2-hydroxycarboxylic acid or its ester represented by ] in the presence of a base. Bases used in the reaction include tertiary aliphatic and aromatic amine compounds such as triethylamine, tributylamine, N-methylmorpholine, pyridine, and lutidine, or potassium lRIII, sodium carbonate,
Basic inorganic compounds such as sodium acetate and potassium acetate, alkali metal alkoxides such as sodium methoxide, sodium ethoxide, and potassium t-butoxide, and alkali metal hydrides such as sodium hydride, potassium hydride, sodium amide, and lithium amide. and alkali metal amides. There are no particular restrictions on the amount of base used, but a catalytic amount is generally sufficient.
The reaction can be carried out without a solvent, but it can also be carried out in a suitable organic solvent that does not affect the reaction.
Examples of organic solvents that can be used include dimethylformamide, dimethylsulfoxide, and acetonitrile. The reaction proceeds satisfactorily under mild conditions near room temperature, but it may also be carried out under flooded conditions. Furthermore, although the reaction proceeds satisfactorily under normal pressure, it can also proceed more efficiently by carrying out the reaction under high pressure. After the reaction is complete, the reaction solution is added to dilute hydrochloric acid, extracted with a solvent that is sparingly soluble in water, such as diethyl ether, ethyl acetate, toluene, or chloroform, and the target product is isolated as crystals by normal post-treatment. However, if necessary, it can be purified by silica gel column chromatography or recrystallization. The 2-hydroxycarboxylic acid represented by the general formula (II) or its ester, which is a raw material used in the reaction, is easily available or can be easily prepared from commercially available raw materials, such as glycolic acid, lactic acid, etc. , 2-
Examples include hydroxyvaleric acid, 2-hydroxyisovaleric acid, and lower alkyl esters thereof. There is no particular restriction on the amount of 2-hydroxycarboxylic acid or its ester used in the reaction, and 3-(24-
The compound of the present invention can be obtained in good yield by using 1 to 20 equivalents to difluoro-5-nitrophenyl-5-isopropylidene-1,3-oxazolidine-2,4-dione. 3-(2,4-difluoro-5-nitrophenyl)- which is another raw material for the reaction
5-isopropylidene-1. 3-Oxazolidine-
2.4-dione can be produced by the following reaction route according to the method described in JP-A-62-174065. <V> (ν1) (VII) [11) (X)
(XI) That is, 2,4-difluoroacetanilide (V) in 3 equivalents or more of oleum,
At a low temperature of -10°C to room temperature, ditrogenization is performed using 1 to 2 equivalents of fuming nitric acid to give 2,4-difluoro-5-nitroacetanilide (m), and then in water or an alcohol solvent, hydrochloric acid or 2,4-difluoro-5-nitroaniline (Vll) can be produced by a conventional deacetylation reaction using acetic acid such as sulfuric acid. Next, this product was converted into 2,4-difluoro-5-nitrophenyl isocyanate (Vll
). There is no particular restriction on the amount of phosgene or phosgene equivalent used, and by using 1 to 10 equivalents of phosgene per ml of aniline derivative, the desired isocyanate derivative (VIII) can be produced in high yield. Obtainable. As the organic solvent, any organic solvent can be used as long as it does not have a harmful effect on the reaction, and examples include ethyl acetate, chloroform, acetonitrile, acetone, N. N-dimethylformamide etc. can be used. In the reaction, an isocyanate derivative can be synthesized by slowly dropping an aniline derivative into a solution of phosgene or a phosgene equivalent at room temperature, and then reacting at a temperature of about 100°C to 100°C under reflux of the reaction solvent.
Isocyanate derivatives (VI
II) in the presence of a base in an incubating solvent to form 2-hydroxy-3
-Carbamate ester (X) can be produced by reacting with methyl-3-putenoate ester. Although the reaction can be carried out under heating, it can proceed satisfactorily even at room temperature, and the desired carbamate ester (X) can be obtained in good yield. Examples of lr solvents include ethers such as diethyl ether, tetrahydrofuran, dioxane, and dimethoxyethane; aromatic solvents such as benzene and toluene; and ethyl acetate, acetonitrile, and N. Solvents such as N-dimethylformamide and dimethyl sulfoxide can be used. As the base, triethylamine, triptylamine, N-methylmorpholine, N. N-dimethylaniline, N. Amines such as N-diethylaniline, pyridine, lutidine, potassium carbonate, sodium carbonate, sodium methoxide,
Alkali metal salts such as potassium t-ptoxide can be used, and the amount of base used is not particularly limited, but a catalytic amount is sufficient. In addition, 2-hydroxy-3-methyl-3-putenoic acid ester has a ratio of 1 to isocyanate (Vll).
By using the same amount or more, the desired carbamate ester (X) can be obtained in good yield. The thus obtained carbamate ester (X) is treated with a base to form the oxazolidine sion derivative (XI), which is the raw material for producing the compound of the present invention, namely 3
-(2,4-difluoro-5-nitrophenyl)-5-
Isopropylidene-1,3-oxazolidine-2.4-
You can get Zion. The reaction is carried out in a normal organic solvent at room temperature to reflux. Examples of organic solvents include ethers such as diethyl ether, tetrahydrofuran, dioxane, and dimethoxyethane, aromatic solvents such as benzene and toluene, or ethyl acetate. , acetonitrile,
Solvents such as N,N-dimethylformamide and dimethyl sulfoxide can be used. As the base, triethylamine, triptylamine, N-methylmorpholine, N,N-dimethylaniline, N. Amines such as N-diethylaniline, pyridine, lutidine, potassium carbonate, sodium carbonate, sodium methoxide, potassium t
- alkali metal salts such as butoxide can be used;
There is no particular limit to the amount of base used, but a catalytic amount is sufficient. In particular, acetonitrile is used as an organic solvent, and potassium carbonate or sodium carbonate is used as a base to produce the desired oxazolidinedione derivative (Xl) in good yield under mild conditions.
This is preferable because it provides the following. Furthermore, 3-(2,4-difluoro-5-nitrophenyl)-5-isobropylidene-1,3-oxazolidine-
In the production of 2.4-dione (Xl), the isocyanate derivative (VIIT) and 2-hydroxy-3-methyl-3-
It can also be produced directly by reaction with butenoic acid ester (IX). [Examples] Hereinafter, the present invention will be explained in more detail with reference to Examples and Reference Examples. Next, a production example of the compound of the present invention will be shown. Production Example 1 3-(2.4-difluoro-5-nitrophenyl)-5-isobropylidene-1.3-oxazolidine-2.4-sion (4.1 g
．． 1 3.6 mmol) and ethyl glycolate (2
Add triethylamine (0 ml) and stir at room temperature.
4 ml) was purified. After further stirring overnight at room temperature, IN hydrochloric acid was added to the reaction mixture. This was mixed with ethyl acetate (20m
The organic layer was washed with water (10 ml x 3). The resulting ethyl acetate solution was dried over anhydrous magnesium sulfate. The dried daisies were filtered off, and the solvent was distilled off under reduced pressure to obtain a yellow oil (6.5 g). This was isolated and purified using silica gel column chromatography and white solid (3
．． 56 g) was obtained. This one is 'H-NMR
According to the results of analysis such as , IR spectrum, etc., it is 1-(2-fluoro-4-ethoxycarbonylmethyloxy-5-nitrophenyl)-5-isopropylidene-1.3-oxazolidine-2.4-dione. confirmed. Melting point = 130-135°C. 'H-NMR spectrum (CDCIs)? 61.28
(3B.t, J-7.5Hz). 2.03 (3H.s
). 2.26 (3H, s). 4.25 (2H.q, J-
7.5Hz), 4.78(28,s). 6.88 (il
l, d, JHF-11.1Hz). 8.99 (11, d
, J [lF-7.5Hz) ppm. IR spectrum (KBr disk): 1820.1740.168
5 cm-' Production Example 2 3-(2,4-difluoro-5-nitrophenyl)-5-isopropylidene-1,3-oxazolidine-2,4-sion (298 g.
1.0 mo+) and ethyl glycolate (104 g.1.
0 mol), and dioxane (500 ml) as a solvent.
and cooled in a water bath while adding sodium amide (3
9 g, 1.0 mol) was slowly added. After no ammonia gas was generated, IN hydrochloric acid (5
00 ml) was added and extracted with ethyl acetate (300 ml××). The organic layer was washed with water (100 ml x 3 times) and dried over anhydrous magnesium sulfate. After the desiccant was filtered off, the solvent was distilled off under reduced pressure, and the resulting solid was recrystallized from ether/hexane to give an almost pure product. 3-(2-fluoro-4-ethoxycarbonylmethyloxy-5-nitrophenyl)
-5-isobropylidene-1,3-oxazolidine-2
．． Example of producing 4-dione (344g, 0.9mol)
3 CHs I 3-(2,4-difluoro-5-nitrophenyl)-5-isobropylideno-1,3-oxazolidine-2,4-sion (4.1 g.
13.6 mmol) and (1) one milk is ethyl (15 ml
) and add triethylamine (4 ml) while stirring at room temperature.
) was added dropwise. After further stirring overnight at room temperature, IN hydrochloric acid was added to the reaction mixture. Add this to ethyl acetate <10ml
The organic layer was extracted with water (5 ml x 3) and washed with water (5 ml x 3).
The resulting ethyl acetate solution was dried over anhydrous magnesium sulfate. The drying agent was filtered off and the solvent was distilled off under reduced pressure to obtain a yellow oil (5.7 g). This was recrystallized from ethyl acetate-hexane to obtain a yellow transparent solid (1.16 g).
From the results of analysis such as LH-NMR and IR spectrum, this product was found to be (+)-3-{2-fluoro-4-(l-ethoxycarbonyl)ethyloxy-5-nitrophenyl}
-5-impropylidene-1,3-oxazolidine-2
, confirmed that it was a 4-dione. Melting point: 148-149°C. 'H-NMR spectrum (CDCI,): 61.27
(3H.t, J-6.6Hz). 1.71 (311.d
．． J-6.3Hz). 2.06 (3H, s), 2.28
(3H, s). 4.23 (211.q, J-6.6Hz
). 4.82 (IH.q.J-6.3Hz). 6.82
(111.d.JBF-11.1Hz). 8.31 (1
8, d, JBF-8.1Hz) ppm. fR spectrum (KBr disk): 1820. 1745.
1725. 1685cm-Ryu production example 4'Pr'Pr3- (2,4-difluoro-5-nitrophenyl)-
5-isopropylidene-1,3-oxazolidine-2,
4-dione (2 9 8 mg. 1. Ommol
), methyl 2-hydroxyisovalerate (1.0 g, 7.
A mixture of 6mmo I) and triethylamine (0.3ml) was reacted overnight at 2500 atm and room temperature using a high-pressure reactor. After the reaction was completed, 0.1N salt # (5
0 mt) and extracted with ethyl acetate (25 ml x 2). The organic layer was washed with water (20 ml x 5) and dried over anhydrous magnesium sulfate. The drying agent was filtered off, and the solvent was distilled off under reduced pressure to obtain a pale yellow oil. This product was isolated and purified using silica gel column chromatography to obtain a colorless oil (319 mg). This one is 'H
-From the results of analysis of NMRS IR spectrum, etc.3-{
It was confirmed that it was 2-fluoro-4-(1-methoxycarbonyl)inbutyloxy-5-nitrophenyl}-5-isobropylidene-1,3-oxazolidine-2,4-dione. '}{-NMR spectrum (CDCI); 6 1.1
0 (6B, d, J-7.OIllz) . 2.05 (3
H,s). 2.27 (3B, s). 2.40 (ILm
). 3.78 (31, s), 4.52 (lH.d, J-
4.0Hz), 6.73(ill, d.JHF-11.
0Hz) ,8.03{11,d,J}IF1l7. O
Hz) ppm. IR spectrum (I[Br dis
k) :1820.1?40.1685 c■1l Example 5 3-(2,4-difluoro-5-nitrophenyl)-5-isopropylidene-1 in a 50 cc eggplant-shaped flask.
．． 3-oxazolidine-2,4-dione (304m
g. 1. 0 2mmo 1) and glycolic acid (2
0 3rng. 2. 67 mmol 1) was added and melted by heating on a 100°C oil bath. Next, triethylamine (0.5 ml) was removed, and the mixture was further stirred at 100°C for 1 hour. IN hydrochloric acid (25 ml) and water (25 ml) were added to the reaction mixture, and the mixture was extracted with ethyl acetate (25 ml x 3). The organic layer was washed with water (25 ml x 3 times) and dried over anhydrous magnesium sulfate. After the desiccant was filtered off, the solvent was distilled off under reduced pressure to obtain a yellow oil. The obtained oil was purified using silica gel column chromatography to obtain 3-(2-fluoro-4-hydroxycarbonylmethyloxy-5-nitrophenyl)-5-isopropylidene-1,3-oxazolidine-2. .4-Sion was obtained. Melting point: 105-110°C. 'H-NMR spectrum (CDCIs-CDsoD)
+6 2.03 (3B.s). 2.30(3Ls)+4
．． 88 (2B, s), 6.97 (ill, d, JHF
-10.0Hz) ,8.07(IH.d, JHF-7
．． OIIz). ppw. ! R spectrum (KBr di
sk): 1820.1740.1680 cm-'Next, 3-(
2. 4-cyfluoro-5-nitrophenyl)-5-
Isobropylidene-1,3-oxazolidine-2,4-
Examples of producing Shion are shown in Reference Examples 1 to 5. Reference example 1? ■N 2594 in a 100cc three-necked flask equipped with a stirrer
Add fuming sulfuric acid (25 ml), and add 2,4-difluoroacetanilide (10 ml) while stirring vigorously under water cooling.
0 g. 5 8. 4 mmol 1) was added little by little and suspended. Subsequently, while cooling with water and stirring vigorously, fuming nitric acid (3 ml) was added dropwise over 30 minutes. After the dropwise addition was completed, the mixture was stirred for 2 hours under water cooling and then at room temperature for 1 hour, and then the reaction mixture was added to ice water with stirring. The precipitated solid was collected by filtration, washed with water, and dried under reduced pressure to obtain a white solid. I
According to H-NMR and IR spectra, this substance is 2,4-
Difluoro-5-nitroacetanilide (10.0 g.
79%). Melting point: 149-150°C, 'H-NMR spectrum (CDCIs): 62.23
(3[1,s), 7. 11 (1B, dd, JHF-10.5,
10.5Hz) ,9.03(1M,dd, JHF-
8.7.8.7Hz). 9.35 (IH.br s
) ppm. IR spectrum (XBr disk)
:3020-3240.1675.1610cm-'Reference Example 2 2,4-difluoro-5 in a 300cc eggplant-shaped flask
-Nitroacetanilide (10.0g, 4 6.3mr
No. 1), methanol (120 ml) and 2N hydrochloric acid (120 ml) were added, and the mixture was stirred under reflux for 2 hours. After the reaction was completed, methanol was distilled off under reduced pressure. The resulting solution was made basic by adding sodium hydrogen carbonate, and ethyl acetate (
100mfx3). The organic layer was diluted with water (50ml
After washing with 3), it was dried with anhydrous magnesium sulfate. After removing the desiccant, the filtrate was concentrated under reduced pressure. The obtained yellow solid was determined by 'H-NMR and IR vectors.
．． 4-difluoro-5-nitroaniline (7.3g.9
1%). Melting point: 97-100°C. IH-NMR spectrum (CDC1*): 63.79
(2B, br s). 6.96 (1B, dd. JHF-11.1, 11
．． LHz), 7.49 (IH.dd, J11F-8.
4.8.411z) ppm, IR spectrum (KBr
disk) :3420.3350.3230.16
00 cm-' Reference Example 3 was added, and while stirring at room temperature, 2,4-difluoro-5-
A solution of nitroaniline (10.0 g, 57.4 mmol) in ethyl acetate (150 ml) was purified over 1 hour and 30 minutes. After the dropwise addition was completed, the mixture was heated to 90°C to remove the solvent and excess phosgene dimer, and a pale brown oil was obtained. This product was confirmed to be almost pure 2,4 difluoro-5-nitrophenyl isocyanate (11.0 g, 96%) by I H +NMR% IR spectrum. 'H-NMR spectrum (CDCIs): 67
．． 18 (I11, dd, JHP-9.6.9.611z
). 7.92 (IH.dd, iF-7.8.7.811
x) PI) II,! R spectrum (κBr di
sk) + 2250 cm - 'Trichloromethyl chloroformate (phosgene dimer; 10.4 ml, 8 6.2 mmo 1) and ethyl acetate (150 ml) in a 500 cc eggplant flask Reference example 4 2.4 in a 300 cc eggplant flask -difluoro-5
-nitrophenyl isocyanate <11.0 g. 48.
6mmo I), 2-hydroxy-3-methyl-3
- Ethyl butenoate (7.7 g. 53.4 mmol) was added and dissolved in diethyl ether (200 ml). To this was added triethylamine (7.4ml.53.1mmol)
) was clarified at room temperature, and after the dropwise addition was completed, the mixture was further stirred for 1 hour. After the reaction was completed, insoluble matter was filtered off, and the filtrate was washed with IN hydrochloric acid.
The ether layer was dried over anhydrous magnesium sulfate and then dried under reduced pressure to obtain a pale yellow solid. This product was purified by silica gel column chromatography (eluent: ethyl acetate/hexane-1/2) to obtain a white solid. This product was found to be almost pure ethyl 2-{N-(2,4-difluoro-5-nitrophenyl)carbamoyloxy}-3-methyl-3-butenoate (14.5 g, 90 %). Melting point: 90-92°C. 'H-NMR spectrum (CDCI): 61.63 (
3H, t, J-6.611z). 1.86 (3H.s
), 4.26 (2H.q.J-6.6Hz). 5.16
(lfl, m), 5.26 (I1+, s), 5.49 (
II {. s), 7.09 (IH, dd, JIIF-9.
3.9.3Hz), 7.13 (IH, br s). 8.92 (IH, dd. JHF-9.0, 9.0tlz
) p9. IR spectrum 0 [Br disk)
:3330.1750.1725 cm-'Reference example 5 2- (N- (2.4
-difluoro-5-nitrophenyl)carbamoyloxy}-3-methyl-3-butenoate (20.0 g, 5
8.1 mmol) and acetonitrile (400 ml)
It was dissolved in Anhydrous potassium carbonate (8 g) was added to this and stirred at room temperature for 1 hour. After the reaction was completed, the solution was acidified with IN hydrochloric acid and extracted with ethyl acetate (700 ml). The organic layer was washed with water and then dried over anhydrous magnesium sulfate. The drying agent was removed and the solution was tied under reduced pressure to yield a yellow oil. Next, methanol was added to this mixture, and upon cooling, the precipitated pale yellow solid was collected by filtration. According to the 'H-NMRS IR spectrum, this solid is 3-(2
．． It was confirmed that it was 4-difluoro-5-nitrophenyl)-5-isobropylidene-1,3-oxazolidine-2,4-sion (15.3 g. 88%). Melting point: 120-121°C. 'H-NMR spectrum (CDCIs): 62. 0
7 (3■.s). 2.30 (3R, s), 7. 26
(18, dd. JHF-9.9. 9.9Hz)
, 7.13 (ILbr s), 8.24 (II, dd. JHF-9.0, 9.0Ilz
) 99m, IR spectrum (WBr disk):
1B15,1745.1685 cm-' Next, Reference Examples 6 to 12 show examples of producing the herbicidally active compound represented by the general formula (III) from the compound of the present invention. 300c equipped with stirrer, dropping funnel and Dimroth
Reduced iron (6.8 g) was placed in a three-necked flask, and then acetic acid (20 ml) was added and heated under reflux until a white suspension was obtained. 3-(2-Fluoro-4-ethoxycarbonylmethyloxy-5-nitrophenyl)-5-isobropylidene-1.3-oxazolidine-2.4-dione (2.76 g, 7.2 mmol) in ethyl acetate (l
Oml) solution was added dropwise under reflux. After the dropwise addition was completed, the mixture was further stirred under reflux for 1 hour, and after cooling, insoluble matter in the system was filtered off. IN hydrochloric acid (50 ml) was added to the resulting solution, and ethyl acetate (
50ml x 3). The organic layer was diluted with water (1
After washing with 0ml x 3), it was dried using anhydrous magnesium sulfate. After removing the desiccant, the solution was distilled off under reduced pressure.
A light brown solid (2.1 g) was obtained. This one is IH-NM
From the results of analysis such as R and IR spectra, 3-(7-fluoro-2H-1,4-penzoxazine-3 (4H)
1-6-yl)-5-isopropylidene-1.3-
It was confirmed that it was txazolidine-2,4-dione. Melting point: 222-223°C. 'H-NMR spectrum (CDCIs-DMSO-dh
): δ2.03 (3H.s), 2.26 (3H.s)
, 4.56 (2H, s). 6.81 (18, d. JHF
-10.5Hz). 6.90 (I11, d.J[IF-
6.0IIz), 7.43(IB.br) ppm, I
R spectrum (lBr disk): 1815.1?
45.1695 cs+-' Reference Example 7 5Qcc equipped with stirrer, dropping funnel and Dimroth
Reduced iron (1.4 g) was placed in a three-necked flask, and then acetic acid (10 ml) was added and the mixture was heated and refluxed until it became a white M turbid solution. A solution of 3-(2-fluoro-4-hydroxycarbonylmethyloxy-5-ditrophenyl)-5-isoprohyritene-1,3-oxazolidine-2,4-dione (168 mg) in acetic acid (l Oml) was refluxed. I cleaned it below. After the dropwise addition was completed, the mixture was stirred at 80°C for 3 hours, and after cooling, insoluble matter in the system was filtered off. Water (50 m
1) was added and extracted using ethyl acetate (20ml x 4). The organic layer was washed with water (20 ml) and dried using anhydrous magnesium sulfate. After removing the drying agent, the solution was evaporated under reduced pressure to obtain a light brown solid (80 mg). This product was found to be 3-(7-fluoro-2H-1,4-benzoxazin-3(4H)mon-6-yl)-5-isobrobylide from the results of analysis such as IH-NMR and IR spectrum. It was confirmed that it was 1,3-oxazolidine-2,4-sion. The melting point, 'H-NMR, and In spectrum are as described in Reference Example 6. Reference example 8 300c equipped with stirrer, dropping funnel and Dimroth
Reduced iron (3.8 g) was placed in a three-necked flask, and then acetic acid (30 ml) was added and heated under reflux until a white suspension was obtained. (4-)-3- (2-fluoro-4-
(1-ethoxycarbonyl)ethyloxy-5-nitrophenyl}-5-isopropylidene-1. 3-oxazolidine-2,4-dione (1.1 g, 2.8 mm
A solution of o 1) in ethyl acetate (20 ml) was clarified under reflux. After the dropwise addition was completed, the mixture was further stirred under reflux for 1 hour, and after cooling, insoluble matter in the system was filtered off. IN hydrochloric acid (50
ml) and extracted with ethyl acetate (50 ml x 3). The organic layer was washed with water (10 ml x 3) and dried using anhydrous magnesium sulfate. After removing the drying agent, the solution was evaporated under reduced pressure to obtain a light brown solid (0.91 g). From the results of analysis such as 'H-NMR and IR spectra, this product is (+)-3-(7-fluoro-2-methyl-2
H-1.4-penzoxazine-3(4H)one-6
-yl)-5-isopropylidene-1,3-oxazolidine-2,4-dione. Melting point: 2
19-220℃. Specific optical rotation: [α'J s-8.21 (20°C, c-1
．． 12. y seton). 'l{-NMR spectrum (CD
Clt): 6 1.59 (3H.d, J-6.3Hz
), 2.04 (311.s), 2.27 (3 [1.s)
, 4.68 (18, q, J-6.3Hz). 648 (I
FI, d, JflF-6.3Hz). 6.85 (1 [
1. d, JHP40.5Hz), 9.20 (111.b
r) ppm. IR spectrum (KBr disk)
:1815.1745.1690 am-'Reference example
9 Add 3-(7-fluoro-2H) to a 25cc eggplant-shaped flask.
-1.4-penzoxazine-3(4H)one-6-
yl)-5-isopropylidene-1,3-oxazolidine-2,4-dione (139 mg, o.4 2 mmo
I) and potassium carbonate (130 mg), and added N.I) and potassium carbonate (130 mg). N-
It was dissolved in dimethylformamide (5 ml). Methyl rhodide (500 μl) was added to the fs solution while stirring at room temperature.
was added dropwise, and the mixture was further stirred at room temperature for 3 hours. IN after reaction completion
Hydrochloric acid was added and extracted with ethyl acetate (2 ml x 3). The organic layer was washed with water (1 ml x 3) and then dried using anhydrous magnesium sulfate. The drying agent was removed and the resulting solution was concentrated under reduced pressure to give a brown oil (250 mg).
I got it. This product was isolated and purified using silica gel column chromatography to obtain a white solid (123 mg).
From the results of analysis such as 'H-NMR and IR spectra, this product is 3-(7-fluoro-4-methyl-2H-1.4
-benzoxazine-3 (4H)mono-6-yl)
-5-Imbropylidene-1,3-oxazolidine-2
．． It was confirmed that it was 4-dione. Melting point: 200-2
01℃. 'H-NMR spectrum (CDCI,)? 62.05
(3Ls). 2.28 (311.s), 3.32 (3H
, s). 4.65 (2H, s). 6.86 (1B, d,
JHF-6.9 [1x). 6.89 (IH.d, JHF
-10.5Hz) ppm. ! R spectrum (KBr
disk): 1825.1730.1690 c Kazuo Sono Reference Example 10 In a 25cc eggplant-shaped flask, add 3-(7-fluoro-2H
-1.4-penzoxazine-3(4H)one-6-
yl)-5-imbropylidene-1,3-oxazolidine-2,4-dione (200 mg.0.6 4 mmo
1) and potassium carbonate (200 mg), and added N.
It was dissolved in N-dimethylformamide (5 ml).
Allyl bromide (500μ
1) was added dropwise, and the mixture was further stirred at room temperature for 4 hours. After the reaction was completed, IN hydrochloric acid was added and the mixture was extracted with ethyl acetate (2 ml x 3). The organic layer was washed with water (lml x 3) and dried using anhydrous magnesium sulfate. The drying agent was removed and the resulting solution was concentrated under reduced pressure to a brown oil (138 m
g) was obtained. This product was isolated and purified using silica gel column chromatography to obtain a white solid (97 mg). From the results of analysis such as 'H-NMR and IR spectra, this product was found to be 3-(4-aryl-7-fluoro-2H-1.
4-penzoxazin-3(4H)mon-6-yl)
-5-inpropylidene-1,3-oxazolidine-2
．． It was confirmed that it was 4-dione. Melting point: 166-1
68℃. 'H-NMR spectrum (CDCI): 62.04 (
3H. s). 2.27 (311, s). 4.51 (2H
, ddd, J-1.5. 1.5.5.1Hz) ,5
．． 19 (111.dat, J-1.4.16.2, 1.
5 [1z). 5.23 (IN, ddt, J-1.4, 7
, 8.1.5Hz). 5.82 (IH.ddk.J-1
6.2.2.7.8.5Hz). 6.85 (IH.d.
JtlF-6.9Hz). 6.88 (1[1.d.JH
F-10.211z) ppm. IR spectrum (KB
r disk) :1810.1740.1690c
m-' Reference example 11 3-(7-fluoro-2H
-1.4-penzoxazin-3(4)mon-6-yl)-5-isobropylidene-1.3-oxazolidine-2.4-cyone (34 7mg, 1.13mmol
) and potassium carbonate (100 mg), and N. It was dissolved in N-dimethylformamide (30 ml). Probargyl bromide (200μ
l) was added dropwise. This mixture was further stirred at room temperature for 5 hours. After the reaction was completed, IN hydrochloric acid was added thereto, and the precipitated crystals were isolated by filtration after being left at room temperature (345 mg
), this product is 3-(7-fluoro-4-probargyl-2H-1,4) from the results of analysis such as 'H-NMR and IR.
-penzoxazine-3(4)mono-6-yl)-5
-isopropylidene-1,3-oxazolidine-2.4
- Confirmed that it was Zeon. Melting point = 194-195°C. 'H-NMR spectrum (CDCIs): 62.03
(3H.s), 2.23 (LH, t, J-2.1Hz)
．． 2.27 (311, a). 4.63 (2■t d*
J-2-IHz) *4.65 (211, s). 6.
90 (1B, d, JHF-9.611z). 7.09 (
IH. d, J■F-6.3Hz) ppm-IR spectrum CKBr disk): 1810.1?40.1
690 c+s-' Reference Example 12 (+)-3-(7-fluoro-2-methyl-2H-1.4-penzoxazine-3) in a 25 cc eggplant-shaped flask.
(4) Mono-6-yl)-5-isobropylidene-1
,3-oxazolidine-2.4-one (1 6 3m
gSO. 5 1 mmol) and potassium carbonate (1
40mg) and N,N-dimethylformamide (
5 ml). Propargyl bromide (300 μl) was added dropwise to the solution while stirring at room temperature. This mixture was further stirred at room temperature for 5 hours. After the reaction was completed, IN hydrochloric acid was added to the mixture, and the mixture was allowed to stand at room temperature, and the precipitated crystals were isolated by filtration (167 mg).
From the results of NMR, IR, etc. analysis, (+)-3-(7-fluoro-2-methyl-4-propargyl-2H-1.4
-penzoxazin-3(4)mon-6-yl)-5
-isobropylidene-1,3-oxazolidine-2.4
- Confirmed that it was Zeon. Melting point: 186-190°C. Specific optical rotation: [α] s-17.00 (20
℃5C~O. S.O. acetone). 'H-NMR spectrum (CDCIs): δ1,5? (3B, d, J-6.
6Hz). 2.03 (3H, s). 2.25 (IH.
t, J-1.5Hz), 2.27(3B,s). 4
．． 63 (2H, d, J = 1.5Hz), 4.68 (IH
．． d, J-6.6}1g), 6.89 (IH.d.JH
F-9.911z). 7.05 (IH.d, JHF-6
．． 5Hz) Pu, IR spectrum CKBr dlsk
): 1810, 1745.1695 c+s-' procedural amendment (voluntary) March 22, 1990 Patent Application No. 56123 of 1999 2. Name of the invention Oxazolidinedione derivatives and their production method 3. Column 5 of "Detailed Description of the Invention" of the amended person's specification. Contents of the amendment (1) "Tokujunsho..." on page 4, lines 4 to 5 of the specification of the present application was changed to rJP-A-1-308278.
and JP-A-1-308211 J. that's all

Claims (2)

[Claims] (1) General formula▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R^1 represents a hydrogen atom or an alkyl group,
R^2 represents a hydrogen atom or a lower alkyl group. ] An oxazolidinedione derivative represented by. (2) 3-(2,4-difluoro-5-nitrophenyl)-5-isopropylidene-1,3-oxazolidine-
2,4-dione and general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (II) [In the formula, R^1 represents a hydrogen atom or an alkyl group,
R^2 represents a hydrogen atom or a lower alkyl group. ] A general formula characterized by reacting a 2-hydroxycarboxylic acid or its ester shown in the presence of a base ▲ There are mathematical formulas, chemical formulas, tables, etc. represents an atom or an alkyl group,
R^2 represents a hydrogen atom or a lower alkyl group. ] A method for producing an oxazolidinedione derivative.